The present invention relates generally to a process for coloring gelatin-based formulations and specifically to a process for preventing the cross-linking between gelatin and the aluminum cations of lake pigments through incorporation of fatty acids.
Gelatin, a collagen-derived protein, is used in a variety of commercial products. For example, gelatin capsules generally are comprised of a gelatin sheath encapsulating a fill of pharmaceutical, nutritional, herbal, or personal care products. The fill may be a liquid, suspension, solid, or semi-solid. For example, see commonly-owned U.S. Pat. Nos. 5,146,730 and 5,459,983, each herein incorporated in their entirety, as examples of using gelatin for enrobing solid products. As another example, for soft gelatin capsules or tablets, the gelatin sheath or shell includes a plasticizer, normally glycerin or sorbitol, to control the softness and flexibility of the sheath. The sheath also includes water, and optionally, other additives, such as flavorants or colorants. Gelatin is used for hard shell encapsulation and dipped products as well. Gelatin is also recognized for use in a variety of food products. For example, soups, canned meats and vegetables, jams, jellies, ice cream, marshmallows, and confectionery items may include a gelatin constituent.
Gelatin formulations (gel masses) may be colored using a variety of water-soluble FDandC and DandC dyes and exempt colorants. In production of multi-tone gelatin capsules (or gelatin-coated cores), the water-soluble dyes tend to bleed, smear, or otherwise become tarnished from the darker (xe2x80x9cstrongerxe2x80x9d) color to the lighter (xe2x80x9cweakerxe2x80x9d) color. Such bleeding particularly occurs across any seam that exists on the gelatin capsule or gelatin-coated core. Similar bleeding problems occur with other gelatin products, as well. Due to the problems associated with certified water-soluble dyes and exempt colorants, lake pigments present a water-insoluble substitute. Lake pigments are known in the art of colorants for edible products. Lake pigments are aluminum or calcium salts of water-soluble FDandC or DandC dyes or exempt colorants, like carmine. The water-soluble dyes and colorants are rendered water insoluble through absorption onto an alumina hydrate substrate. Due to the insolubility of lake pigments in water, the lake pigments color by dispersion. The water-insolubility of lake pigments provides a solution to the aforementioned problems associated with bleeding, smearing, or marking across strong to weak colors.
The use of lake pigments, however, presents other potential negative effects. During manufacturing of gelatin-based formulations and conditioning on heat, aluminum cations (Al+3) are released from the lake pigments. The cations interact (cross-link) with the gelatin causing the gelatin to become thick and tough. Specifically, with respect to gelatin-based capsule manufacture, cross-linked gelatin is unmachineable, i.e., difficult to process on an encapsulating machine. The interaction between the cations and the negatively charged sites along gelatin molecules results in the deleterious cross-linking. The cross-linked gelatin is highly viscous and tough, and for example, the cross-linked tough masses are difficult to cut using the rotary die encapsulation machines known in the art of gelatin capsule manufacture. Further, resulting dried gelatin shells produced from the cross-linked gelatin can exhibit unacceptable delayed disintegration.
U.S. Pat. No. 4,500,453 to Shank discloses cross-linked collagen-derived protein compositions as having increased strength and viscosity. Gelatin is specifically reacted with aluminum salts of acetic acid in order to increase the viscosity of the protein. While the ""453 patent presents such cross-linking (and the associated increase in viscosity) as beneficial, the present inventors, in fact, seek to prevent such interaction as undesirable due to the highly viscous nature and other resulting deleterious properties of the cross-linked protein product.
The extent to which the aluminum cations release from the lake pigments depends on the particular lake pigment. For example, the present inventors have noted that FDandC Red #40 lake exhibits a greater tendency for aluminum cation release. In turn, therefore, when FDandC Red #40 lake is used to color gelatin-based formulations, the resulting colored gelatin-based formulations often are thick and unmachineable.
One solution to the cross-linking problem has been to add a chelating agent, such as ethylenediaminetetraacetic acid (EDTA). The chelating agent approach, however, has been only partially successful in preventing cross-linking. The costs for such agents, as well, prevent this approach from being a preferable solution.
There is a need therefore, for an economical process for coloring gelatin-based formulations with lake pigments that effectively prevents the undesirable cross-linking that occurs between the gelatin-based formulations and the aluminum cations.
The present invention is a process for coloring gelatin-based formulations involving adding a saturated fatty acid to the gelatin along with powdered or granular lake pigment or lake pigment pre-dispersed in glycerin, whereby the saturated fatty acid is added in an amount so as to prevent cross-linking between the gelatin and the aluminum cations released by the lake pigments. Preferably, this amount is about 10% to about 300% by weight of the added lake pigment content. With this process, the resulting colored gelatin-based formulations exhibit acceptable machineability characteristics and disintegration. As an example, the colored gelatin formulation produced by this process has a viscosity of less than approximately 10,000 centipoise (cP) at 60xc2x0 C. Also, specimens (1.5 cm widthxc3x971.5 cm lengthxc3x971.0 cm height) of gelatin-based formulations solidified at ambient temperature disintegrated completely in water (37xc2x0 C.) using standard laboratory disintegration equipment (with a cylindrical disc) within approximately 25 minutes.
Additionally, the present invention is a gelatin-based formulation made from the above-described process. The gelatin-based formulation includes gelatin, lake pigment(s), and a sufficient amount of fatty acid to prevent cross-linking between the gelatin and the cations released from the lake pigment(s). Further, the present invention includes a dosage form that includes the described gelatin-based formulation as the sheath material. The dosage form may encapsulate a liquid, suspension, semi-solid, or solid pharmaceutical, nutritional, herbal, or personal care product, or combination thereof.
These and other aspects of the present invention as disclosed herein will become apparent to those skilled in the art after a reading of the following description of the preferred embodiments.
The present invention is directed to a process for coloring gelatin-based formulations. As used herein, the term xe2x80x9cgelatinxe2x80x9d should be considered to include other polymeric substances, either natural or synthetic, that have negative charges capable of interaction with cations, such as the aluminum cations released by lake pigments. Preferably, the present invention is a process for producing colored gelatin-based formulations suitable for use as a gelatin sheath encapsulating a medicament in a liquid, suspension, solid or semi-solid. However, the invention is applicable to coloring gelatin-based formulations in general.
The preferred gelatin-based capsule sheath composition is characterized by flexibility and a non-tacky consistency. These desired physical characteristics are based upon the formation of capsules using encapsulation machinery. While the gelatin-based formulation must be flexible for machineability, the gelatin-based formulation must also exhibit appropriate integrity to enclose a liquid, suspension, paste, or solid fill material for an extended period of time, e.g., up to about two years, without leakage. Also, the gelatin-based formulation must be soluble upon consumption.
One form of gelatin capsule production known in the art uses a rotary die process in which a molten mass of a gelatin-based sheath formulation is fed from a reservoir onto cooled drums to form two spaced sheets or ribbons of the gelatin-based formulation in a semi-molten state. These ribbons are fed around rollers and brought together at a convergent angle into the nip of a pair of roller dies that include opposed die cavities. The material to be encapsulated is fed into the wedge-shaped joinder of the ribbons. The gelatin ribbons are continuously conveyed between the dies, with portions of the medicament being trapped between the sheets inside the die cavities. The sheets are then pressed together, and severed around each die so that opposed edges of the sheets flow together to form a continuous gelatin-based sheath around the entrapped medicament. The part of the gelatin-based sheath that is severed from the segments forming the capsules is then collected and discarded or recycled. The soft capsules are then dried to increase the integrity of the sheath, and packaged for later distribution and consumption. Other encapsulating machines are equally applicable for gelatin-based formulations prepared using the present invention, such as that disclosed in U.S. Pat. Nos. 5,146,730 and 5,549,983, previously incorporated by reference hereto, and also hard shell capsules and tablets, and gelatin-dipped products as well.
Manufacture of uniform soft gelatin capsules requires a sheath material that has good xe2x80x9cmachineability,xe2x80x9d i.e., it is important that the sheath material be of a non-tacky or non-sticky nature, so that the sheath material can be brought into contact with the rollers without sticking. Further, if the gelatin-based formulation is highly viscous, xe2x80x9cthick,xe2x80x9d and/or tough, it will also affect the machineability of the gelatin sheath material on the encapsulating machine.
The present invention is a process for coloring gelatin-based formulations without sacrificing the machineability of the resulting colored gelatin-based formulations. The process includes adding fatty acids to the gelatin-based formulation in an amount sufficient to prevent cross-linking between the gelatin and the lake pigments. The present inventors propose that fatty acids incorporated into the gelatin mass complex the aluminum cations thereby preventing their reaction with the gelatin. Other phenomena, however, may be applicable and the above theory should not be used to limit the scope of the present invention. Minor amounts of fatty acids have been used in gelatin-coated capsule, caplet, or tablet manufacture to provide slippage of the gelatin away from the die of the encapsulation machine. As described in more detail below, however, the present invention presents a novel use of fatty acids in sufficient amounts so as to adequately complex aluminum cations released from lake pigments.
Although either saturated or unsaturated fatty acids may be used, saturated fatty acids are preferred as more effective at complexing the aluminum cations. Examples of preferred saturated fatty acids are stearic acid, palmitic acid, lauric acid, and myristic acid, and combinations thereof. One particularly preferred fatty acid product contains a minimum content of 40% by weight stearic acid and a minimum content of 40% by weight of palmitic acid. Stauber Performance Ingredients, Inc. of Brea, Calif. distributes such a product under the trade name TRISTAR 149. Any appropriate fatty acid, however, may be used.
Preferably, the fatty acid is added in an amount of about 10% to about 300% by weight of the added lake pigment content. More preferably, the fatty acid is added in an amount of about 80% to about 150% by weight of the added lake pigment content. More preferably, the fatty acid is added in an amount above about 85% by weight of the added lake pigment.